Curcumin prevents paracetamol-induced liver mitochondrial alterations

J Pharm Pharmacol. 2016 Feb;68(2):245-56. doi: 10.1111/jphp.12501. Epub 2016 Jan 15.


Objective: In the present study was evaluated if curcumin is able to attenuate paracetamol (PCM)-induced mitochondrial alterations in liver of mice.

Methods: Mice (n = 5-6/group) received curcumin (35, 50 or 100 mg/kg bw) 90 min before PCM injection (350 mg/kg bw). Plasma activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) was measured; histological analyses were done; and measurement of mitochondrial oxygen consumption, mitochondrial membrane potential, ATP synthesis, aconitase activity and activity of respiratory complexes was carried out.

Key findings: Curcumin prevented in a dose-dependent manner PCM-induced liver damage. Curcumin (100 mg/kg) attenuated PCM-induced liver histological damage (damaged hepatocytes from 28.3 ± 7.7 to 8.3 ± 0.7%) and increment in plasma ALT (from 2300 ± 150 to 690 ± 28 U/l) and AST (from 1603 ± 43 to 379 ± 22 U/l) activity. Moreover, curcumin attenuated the decrease in oxygen consumption using either succinate or malate/glutamate as substrates (evaluated by state 3, respiratory control ratio, uncoupled respiration and adenosine diphosphate/oxygen ratio), in membrane potential, in ATP synthesis, in aconitase activity and in the activity of respiratory complexes I, III and IV.

Conclusions: These results indicate that the protective effect of curcumin in PCM-induced hepatotoxicity is associated with attenuation of mitochondrial dysfunction.

Keywords: aconitase; adenosine triphosphate synthesis; mitochondrial dysfunction; mitochondrial membrane potential; respiratory complexes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaminophen / toxicity*
  • Animals
  • Chemical and Drug Induced Liver Injury / pathology
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Curcumin / administration & dosage
  • Curcumin / therapeutic use*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Liver Function Tests
  • Male
  • Membrane Potential, Mitochondrial / drug effects
  • Mice, Inbred Strains
  • Mitochondria, Liver / drug effects*
  • Mitochondria, Liver / metabolism
  • Mitochondria, Liver / pathology
  • Oxygen Consumption / drug effects
  • Protective Agents / administration & dosage
  • Protective Agents / therapeutic use*


  • Protective Agents
  • Acetaminophen
  • Curcumin